Reactome | DDX58/IFIH1-mediated induction of interferon-alpha/beta

DDX58/IFIH1-mediated induction of interferon-alpha/beta

Stable Identifier

R-HSA-168928

DOI

10.3180/R-HSA-168928.9

Type

Pathway

Species

Homo sapiens

Related Species

Measles virus, Hepatitis C Virus, Rotavirus, Human respiratory syncytial virus A, Influenza A virus

Compartment

mitochondrial outer membrane

Synonyms

RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways

ReviewStatus

5/5

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DDX58/IFIH1-mediated induction of interferon-alpha/beta

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RIG-I-like helicases (RLHs) the retinoic acid inducible gene-I (RIG-I, DDX58) and melanoma differentiation associated gene 5 (MDA5, IFIH1) are RNA helicases that recognize viral double-stranded RNA (dsRNA) present within the cytoplasm (Yoneyama M & Fujita T 2007, 2008). Upon viral infection dsRNA is generated by positive-strand RNA virus families such as Flaviviridae and Coronaviridae, negative-strand RNA virus families including Orthomyxoviridae and Paramyxoviridae, and DNA virus families such as Herpesviridae and Adenoviridae (Weber F et al. 2006; Son KN et al. 2015). Functionally RIG-I (DDX58) and MDA5 (IFIH1) positively regulate the IFN genes in a similar fashion, however they differ in their response to different viral species. DDX58 (RIG-I) is essential for detecting influenza virus, Sendai virus, VSV and Japanese encephalitis virus (JEV), whereas IFIH1 (MDA5) is essential in sensing encephalomyocarditis virus (EMCV), Mengo virus and Theiler's virus, all of which belong to the picornavirus family. RIG-I and MDA5 signalling results in the activation of IKK epsilon and (TKK binding kinase 1) TBK1, two serine/threonine kinases that phosphorylate interferon regulatory factor 3 and 7 (IRF3 and IRF7). Upon phosphorylation, IRF3 and IRF7 translocate to the nucleus and subsequently induce interferon alpha (IFNA) and interferon beta (IFNB) gene transcription (Yoneyama M et al. 2004; Yoneyama M & Fujita T 2007, 2008).

Literature References

PubMed ID	Title	Journal	Year
17395582	Function of RIG-I-like receptors in antiviral innate immunity Yoneyama, M, Fujita, T	J Biol Chem	2007
16214811	Regulation of the type I IFN induction: a current view Honda, K, Yanai, H, Takaoka, A, Taniguchi, T	Int Immunol	2005
17683970	RIG-I family RNA helicases: cytoplasmic sensor for antiviral innate immunity Yoneyama, M, Fujita, T	Cytokine Growth Factor Rev	2007
17942531	Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity Loo, YM, Fornek, J, Crochet, N, Bajwa, G, Perwitasari, O, Martinez-Sobrido, L, Akira, S, Gill, MA, Garcia-Sastre, A, Katze, MG, Gale M, Jr	J Virol	2008
18989317	Viral evasion and subversion of pattern-recognition receptor signalling Bowie, AG, Unterholzner, L	Nat Rev Immunol	2008
18701081	Structural mechanism of RNA recognition by the RIG-I-like receptors Yoneyama, M, Fujita, T	Immunity	2008